CD133⁺PD-L1⁺ cancer cells confer resistance to adoptively transferred engineered macrophage-based therapy in melanoma.

ABSTRACT: Adoptive transfer of genetically or nanoparticle-engineered macrophages represents a promising cell therapy modality for treatment of solid tumor. However, the therapeutic efficacy is suboptimal without achieving a complete tumor regression, and the underlying mechanism remains elusive. Here, we discover a subpopulation of cancer cells with upregulated CD133 and programmed death-ligand 1 in mouse melanoma, resistant to the phagocytosis by the transferred macrophages. Compared to the CD133^-PD-L1^- cancer cells, the CD133⁺PD-L1⁺ cancer cells express higher transforming growth factor-β signaling molecules to foster a resistant tumor niche, that restricts the trafficking of the transferred macrophages by stiffened extracellular matrix, and inhibits th

SUBMITTER: Xu J 

PROVIDER: S-EPMC11751330 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature